Liver injury in acute fatty liver of pregnancy: Possible link to placental mitochondrial dysfunction and oxidative stress

Sathish Kumar Natarajan, Kavitha R. Thangaraj, C. E. Eapen, Anup Ramachandran, Ashis Mukhopadhya, Mathews Mathai, Lakshmi Seshadri, Abraham Peedikayil, Banumathi Ramakrishna, Kunnissery A. Balasubramanian

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Acute fatty liver of pregnancy (AFLP) is a rare disorder which is fatal if not recognized and treated early. Delivery of the feto-placental unit results in dramatic improvement in maternal liver function, suggesting a role for the placenta. However, the mechanisms by which defects in the fetus or placenta lead to maternal liver damage are not well understood and form the focus of this study. Placenta and serum were obtained at delivery from patients with AFLP, and placental mitochondria and peroxisomes were isolated. Placental mitochondrial function, oxidative stress, and fatty acid composition as well as serum antioxidants, oxidative and nitrosative stress markers, and fatty acid analysis were carried out. Hepatocytes in culture were used to evaluate cell death, mitochondrial function, and lipid accumulation on exposure to fatty acids. Oxidative stress was evident in placental mitochondria and peroxisomes of patients with AFLP, accompanied by compromised mitochondrial function. Increased levels of arachidonic acid were also seen in AFLP placenta when compared to control. Patients with AFLP also had a significant increase in oxidative and nitrosative stress markers in serum, along with decreased antioxidant levels and elevated levels of arachidonic acid. These levels of arachidonic acid were capable of inducing oxidative stress in hepatocyte mitochondria accompanied by induction of apoptosis. Exposure to arachidonic acid also resulted in increased lipid deposition in hepatocytes. Conclusion: Oxidative stress in placental mitochondria and peroxisomes is accompanied by accumulation of toxic mediators such as arachidonic acid, which may play a causative role in maternal liver damage seen in AFLP.

Original languageEnglish (US)
Pages (from-to)191-200
Number of pages10
JournalHepatology
Volume51
Issue number1
DOIs
StatePublished - Jan 1 2010

ASJC Scopus subject areas

  • Hepatology

Fingerprint Dive into the research topics of 'Liver injury in acute fatty liver of pregnancy: Possible link to placental mitochondrial dysfunction and oxidative stress'. Together they form a unique fingerprint.

  • Cite this

    Natarajan, S. K., Thangaraj, K. R., Eapen, C. E., Ramachandran, A., Mukhopadhya, A., Mathai, M., Seshadri, L., Peedikayil, A., Ramakrishna, B., & Balasubramanian, K. A. (2010). Liver injury in acute fatty liver of pregnancy: Possible link to placental mitochondrial dysfunction and oxidative stress. Hepatology, 51(1), 191-200. https://doi.org/10.1002/hep.23245